Drug Information

Drug (ID: DG01314) and It's Reported Resistant Information

• Name: Anagrelide
• Synonyms: Anagrelide; 68475-42-3; Anagrelida; Xagrid; Anagrelidum; 6,7-Dichloro-5,10-dihydroimidazo[2,1-b]quinazolin-2(3H)-one; UNII-K9X45X0051; CHEMBL760; 6,7-Dichloro-1,5-dihydroimidazo(2,1-b)quinazolin-2(3H)-one; CHEBI:142290; Imidazo[2,1-b]quinazolin-2(3H)-one, 6,7-dichloro-1,5-dihydro-; K9X45X0051; Anagrelide [INN:BAN]; Anagrelidum [INN-Latin]; Anagrelida [INN-Spanish]; 6,7-Dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2(3H)-one; 6,7-bis(chloranyl)-3,5-dihydro-1H-imidazo[2,1-b]quinazolin-2-one; Imidazo(2,1-b)quinazolin-2(3H)-one, 6,7-dichloro-1,5-dihydro-; C10H7Cl2N3O; HSDB 7325; BL 416201; Anagrelide (INN/BAN); BRN 0619582; 6,7-dichloro-1,5-dihydroimidazo[2,1-b]quinazolin-2[3H]-one; 6,7-Dichlor-1,5-dihydroimidazo(2,1-b)chinazolin-2(3H)-on; 6,7-dichloro-5,10-dihydro-3H-imidazo[2,1-b]quinazolin-2-one; SCHEMBL9411; BIDD:GT0711; GTPL7114; 6,7-dichloro-1,5-dihydroimidazo[2,1-]quinazolin-2(3H)-one; 6,7-dichloro-3,5-dihydroimidazo[2,1-b]quinazolin-2(1H)-one; HMS2089D21; HMS3715J06; HMS3742K13; BCP21314; HY-B0523; ZINC3871541; BDBM50000334; MFCD00866794; AKOS015899342; AKOS016340524; AC-3401; CCG-221242; DB00261; KS-5176; NCGC00161408-02; NCGC00161408-08; NCGC00247665-01; AS-14157; K139; SBI-0206823.P001; DB-055153; CS-0009495; FT-0602855; FT-0630776; D07455; AB00698496-05; AB00698496-07; AB00698496_08; AB01566808_01; 475A423; A915719; Q408163; 6,7-dichloro-3H,5H-imidazo[2,1-b]quinazolin-2-ol; BRD-K62200014-003-05-5; BRD-K62200014-003-08-9; 6,7-Dichloro-1,5-dihydro-imidazo[2,1-b]quinazolin-2-one; 6,7-dichloro-1h,5h-imidazo[2,1-b]quinazoline-2(3h)-one; 6,7-dichloro-1, 5-dihydroimidazo[2,1-b]quinazolin-2[3H]-one; 6,7-Dichloro-1,5-dihydroimidazo[2,1-b]-quinazolin-2(3H)-one; 6,7-dichloro-1,5dihydroimidazo[2,1-b]quinazolin-2[3H]-one; 6,7-dichloro-1H,2H,3H,5H-imidazolidino[2,1-b]quinazolin-2-one; Imidazo[2,1-b]quinazolin-2(3H)-one,6,7-dichloro-1,5-dihydro-; 6,7-di-chloro-1,5-dihydroimidazo[2,1-b]quinazolin-2[3 H ]-one base; 6,7-Dichloro-1,5-dihydro-imidazo[2,1-b]quinazolin-2-one(anagrelide); 6,7-Dichloro-1,5-dihydro-imidazo[2,1-b]quinazolin-2-one(BL-4162A); J33
• Indication:
  In total 2 Indication(s)
  Essential thrombocythemia [ICD-11: 3B63]; Approved; [1]
  Thrombocythemia [ICD-11: 3B63]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Brain cancer [ICD-11: 2A00]; [1]
  Ovarian cancer [ICD-11: 2C73]; [1]
• Target: Phosphodiesterase 3A (PDE3A); PDE3A_HUMAN; [1]
• Formula: C10H7Cl2N3O
• IsoSMILES: C1C2=C(C=CC(=C2Cl)Cl)N=C3N1CC(=O)N3
• InChI: 1S/C10H7Cl2N3O/c11-6-1-2-7-5(9(6)12)3-15-4-8(16)14-10(15)13-7/h1-2H,3-4H2,(H,13,14,16)
• InChIKey: OTBXOEAOVRKTNQ-UHFFFAOYSA-N
• PubChem CID: 135409400
• ChEBI ID: CHEBI:142290
• TTD Drug ID: D0D1HW
• DrugBank ID: DB00261

Type(s) of Resistant Mechanism of This Drug

  RTDM: Regulation by the Disease Microenvironment

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Ovarian cancer [ICD-11: 2C73]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: L1 cell adhesion molecule (L1CAM) [1]

• Resistant Disease: Ovarian cancer [ICD-11: 2C73.0]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Ovarian cancer [ICD-11: 2C73]
• The Specified Disease: Ovarian cancer
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 2.31E-10; Fold-change: -2.89E-01; Z-score: -6.73E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: 22RV1 cells; Prostate; Homo sapiens (Human); CVCL_1045
• Experiment for Molecule Alteration: Puromycin selection and monitored regularly for the maintenance of L1 silencing assay
• Experiment for Drug Resistance: Migration assay
• Mechanism Description: With OVCAR3 cells treated with anagrelide, 2-hydroxy-5-fluoropyrimidine and mestranol , the gap width closure was seen from 48 h onward at all concentrations tested. Similar results were obtained with U251 cells, and L1's metastatic potential is further evidenced by its promotion of epithelial-mesenchymal transition, endothelial cell transcytosis and resistance to chemo- and radiotherapy.

Brain cancer [ICD-11: 2A00]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Regulation by the Disease Microenvironment (RTDM)

Key Molecule: L1 cell adhesion molecule (L1CAM) [1]

• Resistant Disease: Glioblastoma [ICD-11: 2A00.02]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Brain cancer [ICD-11: 2A00]
• The Specified Disease: Brain cancer
• The Studied Tissue: Nervous tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.83E-128; Fold-change: -2.68E-01; Z-score: -2.75E+01
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: MDCK cells; Kidney; Canis lupus familiaris (Dog) (Canis familiaris); CVCL_0422
• Experiment for Molecule Alteration: Puromycin selection and monitored regularly for the maintenance of L1 silencing assay
• Experiment for Drug Resistance: Migration assay
• Mechanism Description: With OVCAR3 cells treated with anagrelide, 2-hydroxy-5-fluoropyrimidine and mestranol , the gap width closure was seen from 48 h onward at all concentrations tested. Similar results were obtained with U251 cells, and L1's metastatic potential is further evidenced by its promotion of epithelial-mesenchymal transition, endothelial cell transcytosis and resistance to chemo- and radiotherapy.

References

• Ref 1: Antagonistic L1 Adhesion Molecule Mimetic Compounds Inhibit Glioblastoma Cell Migration In Vitro .Biomolecules. 2022 Mar 12;12(3):439. doi: 10.3390/biom12030439. 10.3390/biom12030439